The objective of this research is to study the epidemiology of esophageal atresia and tracheo-esophageal fistula (EA/TEF) occurring separately or in combination and to identify the etiologic factors related to the pathogenesis of these conditions. It is hoped that this study will develop a prototype research design for the epidemiologic investigation of other congenital malformations, especially those of the digestive tract and, in particular, malformations in which the teratologic event appears to occur within the first few weeks of gestation. Thus, the focus will be on exposures prior to and around the time of conception rather than later in pregnancy. An in-depth investigation into the epidemiology of EA/TEF will be carried out through a case-control study. Data will be obtained from hospital and physician records and from personal interviews. The characteristics of EA/TEF patients and their families and in particular the frequency of use of a variety of drugs, especially oral contraceptives and other hormonal agents, will be compared with those of control patients and their families to investigate the possibility that environmental factors may be playing a role in the genesis of these conditions. The EA/TEF patients and their families will be compared with two control groups: siblings of the cases and unrelated clinically normal children. A third control group consisting of children with Down's Syndrome will also be included for comparison in order to assess the possible effects of recall bias. In addition, the risks associated with such factors will be examined separately for EA/TEF as well as for isolated EA and for the various anatomic forms of TEF which are observed in human populations. The etiologic findings of this study may provide the foundation for prevention by modifying or eliminating exposure to specific teratogenic factors in the environment.